February 23, 2011 – The Expiration Date for this announcement has been changed to May 8, 2011 per NOT-OD-11-048, which redefines the U01 activity code and announces the transition of U01 applications to electronic submission through Grants.gov using the SF424 (R&R) forms for due dates on or after May 25, 2011.

December 20, 2009 - This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the 06/2009 version of the PHS 398 application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the 11/2007 version of the PHS 398 application forms and instructions.

August 27, 2008 - See Notice (NOT-CA-08-028) The purpose of this Notice is to clarify specific issues pertinent to the scientific scope and requirements.

Purpose. This funding opportunity announcement
(FOA) is designed to promote research on quantitative imaging of tumor response
to cancer therapies in clinical trial settings, with the overall goal of
facilitating clinical decision making. Proposed projects should include the
appropriate development and adaptation/implementation of quantitative imaging
methods, protocols and software solutions/tools (using existing commercial
imaging platforms and instrumentation), and their application in current and
planned Phase 1-2 clinical therapy trials. No support for the clinical trials,
as such, will be provided under this FOA. The proposed projects must focus on
imaging-derived quantitative measurements of responses to drugs and/or
radiation therapy, and/or image-guided interventions. It is anticipated that
these research goals will require multidisciplinary efforts. Therefore, this
FOA solicits applications from multi-disciplinary teams to include oncologists
as well as clinical and basic imaging scientists. The involvement of
industrial partners in the development of the quantitative imaging methods is
not required, but is strongly encouraged. Awardees will form a Quantitative
Imaging Network (QIN) to share ideas and approaches to validate and standardize
imaging data and related imaging metadata for quantitative measurements of
responses to cancer therapies.

Eligible Project Directors/Principal Investigators (PDs/PIs).Individuals with the skills,
knowledge, and resources necessary to carry out the proposed research are
invited to work with their institution/organization to develop an application
for support. Individuals from underrepresented racial and ethnic groups as
well as individuals with disabilities are always encouraged to apply for NIH
support.

Number
of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the
application.

Number
of Applications. Applicants may submit more than one application,
provided that each application is scientifically distinct.

Resubmissions.Applicants may submit a
resubmission application, but such application must include an Introduction
addressing the previous peer review critique (Summary Statement).

Renewals.No
renewal applications will be accepted..

Application
Materials.SeeSection IV.1for application materials.All applications, including resubmission, revision and renewal, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions.

Hearing Impaired. Telecommunications for the hearing impaired are
available at: TTY 301-451-5936.

This
funding opportunity announcement (FOA) is designed to promote research and
development of quantitative imaging methods for the measurement of tumor
response to therapies in clinical trial settings, with the overall goal of
facilitating clinical decision making. Proposed projects should include the
appropriate development and adaptation/implementation of quantitative imaging
methods, imaging protocols, and software solutions/tools (using existing
commercial imaging platforms and instrumentation) and application of these methods
in current and planned Phase 1 and 2 clinical therapy trials. The proposed
projects must be focused on imaging-derived quantitative measurements of
responses to drugs and/or radiation therapy, and/or image-guided interventions
(IGI). It is anticipated that these research goals will require
multidisciplinary efforts. Therefore, this FOA solicits applications from
multi-disciplinary teams to include oncologists as well as clinical and basic
imaging scientists. The involvement of industrial partners in the development
and adaptation/implementation of quantitative imaging methods to aid cancer
therapies is not required, but is strongly encouraged.

In order to
maximize the sharing of ideas and approaches to validate and standardize
imaging data and related metadata for imaging-based quantitative measurements
of tumor responses to cancer therapies, the awardee teams will be required to
participate and collaborate in an NCI-supervised organizational structure to be
called the Quantitative Imaging Network (QIN).

Regarding
the clinical trial component, the FOA will support only the development and
adaptation/implementation of quantitative imaging endpoints (including imaging
methods and related software tools research, and/or informatics infrastructure,
as needed). Eligible clinical trials may be ongoing or planned, but these
trials must be funded through other sources. Therefore, no support for the clinical trials,
as such, will be provided under this FOA.

In addition, in connection with FOA, the NCI will NOT
support

The development of any tumor
imaging hardware components or imaging systems; and

The use of prototype imaging
platforms/instruments for data collection. will be deemed non-responsive to
this FOA.

Alternative/Related
Funding Initiatives

Investigators
seeking support for imaging clinical trials, as such, are referred to the
following initiatives:

Research on early-stage imaging technology development
and testing, can be supported by the traditional NIH R01 or R21 grant
mechanisms.

Background

Challenges for the quantitative assessments of therapeutic
responses. Advances
in molecular medicine offer the potential to move beyond traditional cytotoxic
anticancer treatments and develop safer and more effective targeted therapies
based on molecular characteristics of a patients tumor. This opportunity is
recognized by the NCI Clinical Trials Working Group (CTWG; http://integratedtrials.nci.nih.gov/ict/CTWG_report_June2005.pdf).
However, significanttranslational research efforts are needed to
realize these emerging opportunities. These efforts must include the
development of improved imaging methods and protocols for quantitative
assessments of therapeutic responses. Such quantitative assessment may require
the use of multiple imaging modalities. The development of anatomical,
functional, and molecular imaging methods requires proper recognition and
addressing of the complexities associated with the expression of suspected
biomarkers. Moreover, a full understanding of the response patterns for the
potential surrogate biomarkers (e.g., those used to monitor angiogenesis,
hypoxia, and necrosis) may often require the use of modeling and/or
multiparametric analysis of the image data to examine quantitative correlations
with other clinical metadata and clinical outcomes. These requirements
generally hold for the measurements of tumor responses to drugs or radiation
therapy, and image-guided interventions (IGI). Requirements for these imaging
approaches to aid quantitative measurements of therapeutic response, were
addressed at recent NCI-supported workshops, and in related reports. Specific recommendations
were formulated for measurements of therapeutic responses, using PET (positron
emission tomography) and MRI (magnetic resonance imaging). These
recommendations included, for example, the need for repeat measurements to
determine the minimum changes that can be measured in responses to therapy in a
statistically robust manner. For details, see the following links:http://jnm.snmjournals.org/cgi/reprint/47/6/1059; http://imaging.cancer.gov/reportsandpublications/ReportsandPresentations/MagneticResonance; http://www.rtog.org/; http://www.aaci-cancer.org/irats/pdfs/rider.pdf;
and http://www.rthttp://www.aaci-cancer.org/irats/about_network.aspog.org/.

In addition, the increasing number of experimental oncologic
therapeutic strategies has generated the urgent need to develop reliable and
reproducible methods for early assessment of therapeutic responses. Addressing
these needs is particularly crucial in the context of adaptive clinical trial
design. Oncologists engaged in the development and implementation of clinical
imaging tools and methods are often hampered by an absence of validated quantitative
imaging methods.

Finally, the need for validated quantitative imaging
protocols in oncology will continue to grow. For example, quantitative imaging
data may be increasingly required by regulatory agencies (notably, the U.S.
Food and Drug Administration (FDA; http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html)
as evidence for medical utility (e.g., the efficacy of an experimental cancer
drug). In addition, validated imaging approaches are typically essential to
assess progression free survival (PFS). PFS data are particularly important
for studies of many new targeted therapeutics expected to arrest cancer growth
(but not necessarily eradicate the tumor).

Need for validation of imaging methods for the evaluation of
therapeutic responses. Pertinent to any experimental therapy being investigated in a clinical
trial, there is a need to develop consensus approaches for the harmonization of
quantitative and statistical methods. This harmonization must be conducted for
the collection of imaging data and their analysis across collection sites and
commercial imaging platforms (http://usms.nist.gov/workshops/bioimaging.htm).
Various performance characteristics such as signal-to-noise ratio,
contrast-to-noise ratio, and spatial or temporal resolution of different
devices and modalities are often platform dependent. Moreover, the performance
of these platforms may often fluctuate (reflecting possible instrument drift)
during the course of therapy to be monitored. The development and
implementation of appropriate quantity control methods, especially those using
imaging phantoms, is thus a critical requirement. This approach often includes
the use of a single, multi-functional phantom or an array of phantom designs
that reflect measurements based on anatomy, specific function(s), and/or
specific biomolecules(s). These phantoms may be either physical or
computer-simulated. Both kinds are often designed and utilized to reveal
temporal fluctuations in instrument performance. The phantom-based
measurements and their evaluation are thus vitally important when the
variability in instrument performance might approach the expected magnitude of
the biological parameters to be measured as responses to therapy.

Need for clinical decision software tools. Quantitative imaging data that
reflect responses to therapy and are correlated with clinical outcomes can
provide an important basis for clinical decisions. In principle, the
quantitative and objectively assessed characteristics derived from imaging
experiments should be superior to the traditional, subjective (i.e.,
observer-based) assessments that often have high inter- and intra-observer
variability. Further efforts are warranted to replace the subjective approaches
with the objective assessments, Therefore, there is a critical need to develop
and validate algorithms that can process collected imaging data to generate
clinical knowledge for decision-making, and ideally automatically. Such
algorithms are often referred to as clinical decision tools. These software
tools usually involve the extraction of computed spatial features from images
(generated by anatomical, functional, and/or molecular imaging methods) and/or
the use of modeling methods that include both spatial and temporal
characteristics. The algorithms typically have many interrelated parameters
that need to be optimized prior to their use in specific clinical trials. This
optimization is usually achieved through access to image databases that include
pathological results or expert radiologist readings or other validation
estimates such as comparison to simulated image sets. Used retrospectively,
these validated data archives can be parsed in many different ways to create
training and test data sets needed to benchmark the relative performance of
algorithms and their clinical decision-making ability. Ideally, these datasets
can be available as public archives to encourage development of more
standardized methods for evaluation of clinical decision tools (go to http://ncia.nci.nih.gov/collections/).Finally, there is an opportunity to leverage support from industry, under a
public-private partnership, to expand these databases for the purpose of more
timely FDA approval and broad dissemination of clinical decision tools and
related informatics infrastructure (http://www.fnih.org/partners/research_environment/IDRI.shtml).

Need for the standardization of software architecture. The performance of a clinical
decision tool based on quantitative imaging often depends on the specific
imaging platform for which it was created. This lack of transportability
reduces acceptance of the quantitative methods and obscures validation
procedures. One way to minimize this problem is to implement standardized open
computer software architecture (one permitting plug and play software tools)
for quantitative imaging tools. One of the main efforts to standardize all
aspects of medical imaging and insure inter-operability is the Digital Imaging
and Communications in Medicine (DICOM; http://medical.nema.org/dicom/geninfo/Brochure.pdf).
DICOM Working Group 23, for example, is currently developing such standards to
support inter-operability of software tools for data collection and analysis
across different imaging platforms (http://medical.nema.org/Dicom/minutes/Committee/2004/2004-09-03/Approved_Work_Items/DICOM_Plug-ins_06.doc).
The extension of the DICOM standard for application hosting, if approved,
will reduce the dependence of software tools on specific platform
configurations and will help accelerate the dissemination of commercial
software tools that are FDA approved. It would be ideal to extend the
applicability of the emerging standard to the clinical setting..

In connection with the cancer Biomedical Informatics Grid
(caBIG)(https://cabig.nci.nih.gov/overview/),
the NCI is currently supporting an open architecture/open source environment
initiative, In Vivo Imaging Workspace (https://cabig.nci.nih.gov/workspaces/Imaging).
This Imaging Workspace is based on an open architecture environment. It permits
plug and play tools for image query, image annotation, and markup, including
web-based validation of tools for image analysis using the caBIG. Several
imaging companies are also exploring alternative proprietary software
architectures that will potentially conform to the open architecture approach.
This initiative is expected to aid efforts to develop standardized methods for
validation of clinical decision tools and to assess their performance using
publicly accessible archives.

Specific Goals and Requirements

General Scope of the Projects. Projects proposed in response to this FOA must be designed to develop
state-of-the-art quantitative methods and for monitoring therapeutic
responses. The proposed quantitative imaging methods should be based on
imaging of responses to any form of oncologic therapy (namely drugs, radiation
therapy, or image guided interventions [IGI]). Projects may span the
development in the research settings, translation, and validation as needed,
and incorporation of these solutions as endpoints into imaging protocols for
current and planned Phase 1 and 2 trials in the clinical setting. The
validation of imaging methods for the evaluation of therapeutic responses
should be included. However, projects limited only to the validation aspects
of imaging methods are NOT appropriate for this FOA. All of the proposed
projects must include testing new or emerging imaging protocols and
quantitative imaging methods in early phase trials (funded by other sources).
All these solution/tools must be suitable for use as clinical decision software
tools.

Multidisciplinary Teams. Ideally,
the multi-disciplinary teams will be created to include both basic imaging
research groups and clinical researchers (either within the same institution or
from different institutions) as necessary to ensure that the appropriate
experience in both early phase clinical trials and advanced quantitative
imaging methods is achieved. Participants may include, for example, academic
centers of excellence in computer science, medical physics or bioengineering,
with specific experience in quantitative imaging methods, clinical decision
software tools, and related informatics infrastructure. The clinical sites for
data collection may include (but are not limited to) NCI-designated Cancer
Centers, Specialized Programs of Research Excellence (SPOREs) or co-operative
clinical trials group(s) that actively participate in the use of imaging
methods in Phase 1 and Phase 2 therapy trials. The inclusion of industrial
partners is strongly encouraged to help develop a broad consensus on the
implementation of quantitative imaging methods/software tools that would be
applicable across different imaging platforms.

To facilitate
multidisciplinary interactions, applicants are encouraged to use the multiple
Project Directors/Principal Investigators (PDs/PIs) option (see Section IV.2). If this option is used, it is expected
that one of the PIs will be designated as lead PI. The lead PI can be
affiliated with an imaging researcher (basic or translational), a clinical
researcher, or a researcher from industry, as appropriate.

In light of the advances
being made with multimodal imaging, it is anticipated that applicant teams may
propose research that incorporates quantitative imaging protocols and methods
for several imaging modalities, including anatomical, functional and molecular
imaging, While this is acceptable, it is recognized that focusing on a single
imaging modality by a multi-site team can also be fruitful.

Research Areas. It is strongly suggested that the proposed research
plan follows the strategy listed below, with the understanding that emphasis in
each area may vary depending on the selection of clinical trial(s) and imaging
modalities.

a) The identification of drug,
radiation therapy, and/or IGI trials that would benefit from quantitative imaging
methods and improve prognostic outcome, including the development and
optimization of clinical trial protocols, specifically to implement
quantitative imaging methods;

b) The development of quality
assurance methods to test and characterize time related changes in imaging
systems and IGI platforms during the course of therapy;

c) The development of algorithms,
modeling and image simulation methods, and related databases to validate
clinical decision software tools with the goal of improving the ability to
measure the response of targeted tumors to therapy quantitatively. Ideally,
these tools should be developed for a range of imaging methods and validated
against existing public web accessible databases. The intent is to explore
consensus methods for validating clinical decision tools. See Section VI.
2.A.3 regarding the function of the Steering Committee in this regard for the
QIN.

d) The development of software
architecture, designed to allow interoperability of software tools that may
include open source approaches. The long-term goal should ideally include
harmonizing data collection, analysis, and image display across different
commercial imaging, therapy, and IGI platforms. Equivalent methods such as
proprietary methods and solutions supported by industry are appropriate. All
the methods proposed should ideally meet emerging NCI caBIG requirements and/or
DICOM 23 requirements, if and when available.

To meet the goals of this
FOA, each applicant team is expected to
engage oncologists in the evaluation process to accept quantitative imaging for
clinical decision making in clinical trials for appropriately targeted
therapies. Examples of appropriate research goals to be accomplished by the
end of year 5 of the projects include (but are not limited to) the following:

a) Completion of quantitative
imaging studies incorporated into two or more Phase 1 and 2 clinical trials.
This goal must properly address the important aspects of patient accrual and
data analyses. Validation with patient outcome can take significantly longer
than the duration of this program.

b) Improved consensus and
rationalization for employing and optimizing quantitative, multi-modal, and
molecular imaging methods for therapies where they are clinically useful;

c) Public registries and image database
resources to support clinical decision making for therapies by the broader
oncology community (i.e., NCI Community Cancer Centers Program [NCCCP], NIH
Clinical Trial Science Awards, etc.); and

d) Replacement of observer or
qualitative estimates of therapy response, such as the use of the RECIST
(Response Evaluation Criteria in Solid Tumors) criteria.

Plans for progressive
validation of these components for targeted of Phase 1 and 2 trials must also
be described.

Awarded teams will be
formed into a network for the purpose of sharing plans for validation and
standardization of the assessment of the performance of software tools and to
report clinical results in the use of quantitative imaging as a measure of
therapy response. The network will be governed by a steering committee as
described in Section VI 2.A.3 of this FOA.

The
use of validation methods and software tools in response to this FOA must
address the issue of compatibility with the NCI caBIG informatics initiative https://cabig.nci.nih.gov/). One of the
goals of the caBIG (specifically, the caBIG imaging archive and workspace
initiative) is to stimulate the development of open source informatics tools
and open access to bioinformatics resources and data bases. These attributes
should facilitate data integration and analysis over a broad range of data
collection platforms covering imaging, genomic, and proteomic resources.
Compatibility with caBIG components will aid investigators to consider the importance
of other longitudinal biomarker data in response to therapy. This will give
greater breadth to the research applicability. (https://imaging.nci.nih.gov/ncia/).

During the course of this
program, the NCI may exlore the possibility of creating a Public-Private
Partnership (PPP) with the imaging and pharmaceutical industry communities to
be mediated through the Foundation NIH (FNIH, http://www.fnih.org/.
The long-term goal and rationale for this PPP would be the creation of an
extended public database and related resources of image data, meta-data, and
clinical outcome data collected from sites that are funded through the FOA.
These resources could be leveraged through the PPP to facilitate more timely
FDA approval of industrys clinical decision tools: http://www.fnih.org/.

U.S. applicants requesting more than
$250,000 in annual direct costs and all foreign applicants must complete and
submit budget requests using the Research & Related Budget component.

Thisis a
cooperative agreement award mechanism. In the cooperative agreement mechanism,
the Project Director/Principal Investigator (PD/PI) retains the primary
responsibility and dominant role for planning, directing, and executing the
proposed project, with NIH staff being substantially involved as a partner with
the Principal Investigator, as described under the Section VI. 2. Administrative
Requirements,
"Cooperative Agreement Terms and Conditions of Award."

The NCI intends to reissue this funding opportunity
after the closing date for this present opportunity.

2. Funds Available

Because
the nature and scope of the proposed research will vary from application to
application, it is anticipated that the size and duration of each award will
also vary. Although the financial plans of the IC(s) provide support for this
program, awards pursuant to this funding opportunity are contingent upon the
availability of funds.

It
is required that requests for support submitted in response to this FOA should
not exceed $500,000 (direct costs) per year. Facilities and administrative
costs requested by consortium participants are not included in the direct cost
limitation (see NOT-OD-05-004).

The
decision of whether to apply for a grant with a single PD/PI or multiple
PDs/PIs is the responsibility of the investigators and applicant organizations
and should be determined by the scientific goals of the project. Applications
for grants with multiple PDs/PIs will require additional information, as
outlined in the instructions below. When considering multiple
PDs/PIs, please be aware that the structure and governance of the PD/PI
leadership team as well as the knowledge, skills, and experience of the
individual PDs/PIs will be factored into the assessment of the overall
scientific merit of the application. Multiple PDs/PIs on a project share the
authority and responsibility for leading and directing the project,
intellectually and logistically. Each PD/PI is responsible and
accountable to the grantee organization, or, as appropriate, to a collaborating
organization, for the proper conduct of the project or program, including the
submission of required reports. For further information on multiple PDs/PIs,
please seehttps://grants.nih.gov/grants/multi_pi.

Applicants may submit a
resubmission application, but such application must include an Introduction
addressing the previous peer review critique (Summary Statement). Since this is
a new FOA, this provision is not applicable to
the first receipt cycle after FOA release.

No
renewal applications will be accepted.

Applicants
may submit more than one application, provided that each application is
scientifically distinct.

Applications must be
prepared using the most current PHS 398 research grant application instructions
and forms. Applications must have a D&B Data Universal Numbering System
(DUNS) number as the universal identifier when applying for Federal grants or
cooperative agreements. The D&B number can be obtained by calling (866)
705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should
be entered on line 11 of the face page of the PHS 398 form.

The title and number of
this funding opportunity must be typed in item (box) 2 only of the face page of
the application form and the YES box must be checked.

Every effort should be made to comply with the
format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.

Funds for up to 8% Facilities and administrative
(F&A) costs (excluding equipment) may be requested. SeeNOT-OD-01-028, March 29,
2001.

Organizations must comply with Federal/NIH
policies on human subjects, animals, and biohazards.

Organizations must comply with Federal/NIH
biosafety and biosecurity regulations. See Section VI.2., Administrative and
National Policy Requirements.

Proposed
research should provide special opportunities for furthering research programs
through the use of unusual talent, resources, populations, or environmental
conditions in other countries that are not readily available in the U.S. or that augment existing U.S. resources.

SPECIAL
INSTRUCTIONS

Applications
with Multiple PDs/PIs

When multiple PD/PIs are
proposed, use the Face Page-Continued page to provide Items 3a 3h for all
PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all
communications between the PD/PIs and the agency. The contact PD/PI must meet
all eligibility requirements for PD/PI status in the same way as other PD/PIs,
but has no special roles or responsibilities within the project team beyond
those mentioned above. The contact PD/PI may be changed during the project
period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face
Page), with all additional PD/PIs listed on Form Page 1-Continued. When
inserting the name of the PD/PI in the header of each application page, use the
name of the Contact PD/PI, et. al. The contact PD/PI must be from the
applicant organization if PD/PIs are from more than one institution.

All individuals designated
as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI
role in that system (other roles will not give the PD/PI the appropriate access
to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing
Multiple PDs/PIs will be required to include a new section describing the
leadership plan approach for the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the research plan, entitled Multiple PD/PI Leadership Plan must be
included. A rationale for choosing a multiple PD/PI approach should be
described. The governance and organizational structure of the leadership team
and the research project should be described, and should include communication
plans, process for making decisions on scientific direction, and procedures for
resolving conflicts. The roles and administrative, technical, and
scientific responsibilities for the project or program should be delineated for
the PDs/PIs and other collaborators.

If
budget allocation is planned, the distribution of resources to specific
components of the project or the individual PDs/PIs should be delineated in the
Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award (NOA).

Applications
must be prepared using the research grant application forms found in the PHS
398 instructions for preparing a research grant application. Submit a signed,
typewritten original of the application, including the checklist, and three
signed photocopies in one package to:

The NIH will not
accept any application in response to this funding opportunity that is
essentially the same as one currently pending initial merit review unless the
applicant withdraws the pending application. The NIH will not accept any
application that is essentially the same as one already reviewed. However, the
NIH will accept a resubmission application, but such application must include
an Introduction addressing the critique from the previous review.

All NIH awards
are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants Policy Statement.

Pre-award costs
are allowable. A grantee may, at its own risk and without NIH prior approval,
incur obligations and expenditures to cover costs up to 90 days before the
beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the
project; and 2) would be allowable under the grant, if awarded, without NIH
prior approval. If specific expenditures would otherwise require prior
approval, the grantee must obtain NIH approval before incurring the cost. NIH
prior approval is required for any costs to be incurred more than 90 days
before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project
(see the NIH Grants Policy Statement at https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

Awardees must agree to attend two
meetings annually in the Washington, DC, area and to agree to the Cooperative
Agreement Terms and Conditions of Award in Section VI.2.A, Award
Administration Information.

Investigators
should budget for travel to two investigator meetings per year to be held in
the Washington, DC, area. These 1-day meetings of the QIN Steering Committee
will be held for the purpose of disseminating information regarding progress on
incorporating quantitative imaging into clinical trials and other topics of
interest as stated in published agendas distributed by the NCI staff before the
meetings.

Do not use the Appendix to circumvent the page limitations. An application that does not observe the required page limitations
may be delayed in the review process.

Resource Sharing
Plan(s)

NIH
considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value of, and advance,
research. When resources have been developed with NIH funds and the associated
research findings published or provided to NIH, it is important that they be
made readily available for research purposes to qualified individuals within
the scientific community. If the final data/resources
are not amenable to sharing, this must be explained in Resource Sharing section
of the application (see https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

(b) Sharing Model Organisms: Regardless of
the amount requested, all applications where the development of model organisms
is anticipated are expectedto include a description of a
specific plan for sharing and distributing unique model organisms and related
resources, or state appropriate reasons why such sharing is restricted or not
possible (see Sharing Model Organisms Policy and NIH Guide NOT-OD-04-042).

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount
requested, applicants seeking funding for a genome-wide association
study are expected to provide a plan for submission of GWAS data to the
NIH-designatedGWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible. A
genome-wide association study is defined as any study of genetic variation
across the entire genome that is designed to identify genetic associations with
observable traits (such as blood pressure or weight) or the presence or absence
of a disease or condition. For further information, see Policy for
Sharing of Data Obtained in NIH-Supported or -Conducted Genome-Wide Association
Studies (NIH Guide NOT-OD-07-088 and https://grants.nih.gov/grants/gwas/).

caBIG
Compatibility: The use of validation methods and software tools in
response to this FOA must address the issue of compatibility with the NCI caBIG
(cancer Biomedical Informatics Grid) informatics initiative (https://cabig.nci.nih.gov/). One of the
goals of the caBIG (specifically the caBIG imaging archive and workspace
initiative) is to stimulate the development of open source informatics tools
and open access to bioinformatics resources and data bases. Applications will
be reviewed, but not scored, on their compatibility with caBIG and National
Cancer Imaging Archive (NCIA).

Specific
Instructions for Foreign Applications

All
Foreign applicants must complete and submit budget requests using the Research
& Related (R&R) Budget component found in the application package for
this FOA (see NOT-OD-06-096, August
23, 2006).

Section V. Application
Review Information

1.
Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria
described below will be considered in the review process.

2.
Review and Selection Process

Applications
that are complete will be evaluated for scientific and technical merit by an
appropriate peer review group convened by the NCI and in accordance with NIH
peer review procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below.

As part
of the scientific peer review, all applications will:

Undergo a
selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned an impact/priority score;

Receive a
written critique; and

Receive a second level of review by the National
Cancer Advisory Board.

Applications
submitted in response to this funding opportunity will compete for available
funds with all other recommended applications. The following will be
considered in making funding decisions:

Scientific
and technical merit of the proposed project as determined by scientific
peer review;

Availability
of funds; and

Relevance
of the proposed project to program priorities.

The
goals of NIH supported research are to advance our understanding of biological
systems, to improve the control of disease, and to enhance health. In their
written critiques, reviewers will be asked to comment on each of the following
criteria in order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals. Each of these criteria
will be addressed and considered in assigning the overall score, and weighted
as appropriate for each application. Note that an application does not need to
be strong in all categories to be judged likely to have major scientific impact
and thus deserve a meritorious impact/priority score. For example, an investigator may
propose to carry out important work that by its nature is not innovative but is
essential to move a field forward.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance: Does this study address an
important problem? If the aims of the application are achieved, how will
scientific knowledge or clinical practice be advanced? What will be the effect
of these studies on the concepts, methods, technologies, treatments, services,
and/or preventative interventions that drive this field?

In addition, specific for this FOA: Does the
proposed research plan of the multi-disciplinary research team address translational
research and provide quantitative imaging methods, and/or research resources as
required for the advancement of the role of quantitative imaging as a biomarker
for response to therapy?

Investigator(s): Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, specific for this FOA: Is there
evidence that the research team members can work together effectively? Does
the multi-disciplinary team have experience in quantitative imaging and in
clinical trials?

Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, specific for this FOA: Does the
proposed research team address innovative solutions for the role of
quantitative imaging as a biomarker? Are the proposed Phase 1 and 2 clinical
trials appropriate examples to substantiate the need for these methods?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

In addition, specific for this FOA: Does the
proposed multi-disciplinary research plan utilize the unique skills and
capabilities of the academic and clinical centers, including industry partners
if proposed? How well can the participating research centers support the
conduct of the translational research for the optimization and implementation
of quantitative imaging methods as applied to therapy response?

Environment: Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, specific for this FOA: Do the
participating research and clinical centers demonstrate adequate commitment to
this project?

Additional Review Criteria

As applicable for the project
proposed, reviewers will consider the following additional items in the
determination of scientific and technical merit, but will not give separate
scores for these items.

Protections for Human Subjects. For
research that involves human subjects but does not involve one of the six
categories of research that are exempt under 45 CFR Part 46, the committee will
evaluate the justification for involvement of human subjects and the proposed
protections from research risk relating to their participation according to the
following five review criteria: 1) risk to subjects, 2) adequacy of protection
against risks, 3) potential benefits to the subjects and others, 4) importance
of the knowledge to be gained, and 5) data and safety monitoring for clinical
trials.

For research that involves human subjects and meets
the criteria for one or more of the six categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate: 1) the justification for the
exemption, 2) human subjects involvement and characteristics, and 3) sources of
materials.

Inclusion of Women, Minorities, and Children.
When the proposed project involves clinical research, the committee will
evaluate the proposed plans for inclusion of minorities and members of both
genders, as well as the inclusion of children.

Vertebrate Animals. The committee
will evaluate the involvement of live vertebrate animals as part of the
scientific assessment according to the following five points: 1) proposed use of
the animals, and species, strains, ages, sex, and numbers to be used; 2)
justifications for the use of animals and for the appropriateness of the species
and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting
discomfort, distress, pain and injury to that which is unavoidable in the
conduct of scientifically sound research including the use of analgesic,
anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and
5) methods of euthanasia and reason for selection if not consistent with the
AVMA Guidelines on Euthanasia.

Resubmission Applications. When
reviewing a Resubmission application (formerly called an amended application),
the committee will evaluate the application as now presented, taking into
consideration the responses to comments from the previous scientific review
group and changes made to the project.

Renewal Applications. When reviewing
a Renewal application (formerly called a competing continuation application),
the committee will consider the progress made in the last funding period.

Revision Applications. When
reviewing a Revision application (formerly called a competing supplement
application), the committee will consider the appropriateness of the proposed
expansion of the scope of the project. If the Revision application relates to a
specific line of investigation presented in the original application that was
not recommended for approval by the committee, then the committee will consider
whether the responses to comments from the previous scientific review group are
adequate and whether substantial changes are clearly evident.

Biohazards. Reviewers will assess
whether materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

In addition to the above
criteria, the following items will continue to be considered in the
determination of scientific merit and the rating:

Resubmission
Applications (formerly revised/amended applications): When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project. Remove if not applicable

Protections for Human Subjects: For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children: When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals: The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Biohazards: If materials or procedures
are proposed that are potentially hazardous to research personnel and/or the
environment, determine if the proposed protection is adequate.

Additional Review Considerations

As applicable for the
project proposed, reviewers will address each of the following items, but will
not give scores for these items and should not consider them in providing an
overall impact score.

Budget and Period Support. Reviewers
will consider whether the budget and the requested period of support are fully
justified and reasonable in relation to the proposed research.

Select Agents Research. Reviewers
will assess the information provided in this section of the application,
including 1) the Select Agent(s) to be used in the proposed research, 2) the
registration status of all entities where Select Agent(s) will be used, 3) the
procedures that will be used to monitor possession use and transfer of Select
Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security
of the Select Agent(s).

Applications from Foreign Organizations.
Reviewers will assess whether the project presents special opportunities for
furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions that exist in other countries and
either are not readily available in the United States or augment existing U.S.
resources.

Budget: The reasonableness of the
proposed budget and the requested period of support in relation to the proposed
research. The impact/priority score should not be affected by the evaluation of the
budget.

Applications
from Foreign Organizations: Whether the project presents special opportunities
for furthering research programs through the use of unusual talent, resources,
populations, and/or environmental conditions in other countries that are not
readily available in the United States or that augment existing U.S. resources will be assessed.

2.C.
Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment
on the reasonableness of the following Resource Sharing Plans, or the rationale
for not sharing the following types of resources. However, reviewers will not
factor the proposed resource sharing plan(s) into the determination of
scientific merit or impact/priority score, unless noted otherwise in the FOA. Program
staff within the IC will be responsible for monitoring the resource sharing; go
to the following Web sites for more information:

caBIG
Compatibility: The use of validation methods and software tools in
response to this FOA must address the issue of compatibility with the NCI caBIG
(cancer Biomedical Informatics Grid) informatics initiative (https://cabig.nci.nih.gov/). One of the
goals of the caBIG (specifically the caBIG imaging archive and workspace
initiative) is to stimulate the development of open source informatics tools
and open access to bioinformatics resources and data bases. Applications will
be reviewed, but not scored, on their compatibility with caBIG and National
Cancer Imaging Archive (NCIA).

3. Anticipated Announcement and Award
Dates

Not Applicable.

Section
VI. Award Administration Information

1. Award Notices

After the peer review
of the application is completed, the PD/PI will be able to access his or her
Summary Statement (written critique) via the eRA Commons.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NOA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs (see also Section IV.5. Funding Restrictions).

A
formal notification in the form of an NoA will be provided to the applicant
organization. The NoA signed by the grants management officer is the
authorizing document. Once all administrative and programmatic issues have been
resolved, the NoA will be generated via email notification from the awarding
component to the grantee business official (designated in Item 12 on the
Application Face Page). If a grantee is not email enabled, a hard copy of the
NoA will be mailed to the business official.

The
following Terms and Conditions will be incorporated into the award statement
and will be provided to the Principal Investigator as well as to the
appropriate institutional official, at the time of award.

2.A. Cooperative Agreement
Terms and Conditions of Award

The following special
terms of award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS grant administration regulations at 45 CFR Parts
74 and 92 (Part 92 is applicable when State and local Governments are eligible
to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for
this program will be the cooperative agreement, an "assistance"
mechanism (rather than an "acquisition" mechanism), in which
substantial NIH programmatic involvement with the awardees is anticipated
during the performance of the activities. Under the cooperative agreement, the
NIH purpose is to support and stimulate the recipients' activities by
involvement in and otherwise working jointly with the award recipients in a
partnership role; it is not to assume direction, prime responsibility, or a
dominant role in the activities. Consistent with this concept, the dominant role
and prime responsibility resides with the awardees for the project as a whole,
although specific tasks and activities may be shared among the awardees and the
NIH as defined below.

The PD/PIs will have primary authority and
responsibility to define objectives and approaches, and to plan, conduct,
analyze, and publish results, interpretations, and conclusions of studies
conducted under this program. The PDs/PIs assume responsibility and
accountability to the applicant organization officials and to the NCI for the
performance and proper conduct of the research supported by the U01 award in
accordance with these terms and conditions of the award.

Specific rights and responsibilities will include the following:

The PDs/PIs will
be responsible for the organization and scientific/technical direction of their team(s);

The PDs/PIs will
identify potential problem areas during the course of the program and
implementing corrective action;

Lead PDs/PIs
will be participate as a members of the steering committee for the overall
network (which includes participation in monthly teleconference calls and
traveling to the Washington, DC, area for semi-annual network meetings);

Awardees
will be responsible for the proper compatibility of the project informatics
with the NCI caBIG (cancer Biomedical Informatics Grid) informatics initiative
(https://cabig.nci.nih.gov/)
and National Cancer Imaging Archive (NCIA). and

The
Awardees must agree to abide by the decisions of the Steering Committee.

Awardees
will retain custody of and have primary rights to the data and software
developed under these awards, subject to Government rights of access consistent
with current HHS, PHS, and NIH policies.

2.A.2. NIH
Responsibilities

The Chief of the
Imaging Technology and Development Branch of the Cancer Imaging Program of NCI
and the designated Program Director will have substantial programmatic
involvement that is above and beyond the normal stewardship role in
awards, as Project Scientist and Project Coordinator, respectively (as
described below). Additionally, the Program Director serving as Project
Coordinator will be responsible for the normal scientific and programmatic
stewardship of the award and will serve as Program Official named in the award
notice. The NCI
Project Scientist and Coordinator (and other substantially involved staff
members that may be designated) will not attend peer review meetings of renewal
(competing continuation) and/or supplemental applications. If such
participation is deemed essential, these individuals will seek NCI waiver
according to the NCI procedures for management of conflict of interest.

The main NCI responsibilities pertinent to the awards
under this FOA include the following activities:

Participation of the NCI Project Scientist
and Project Coordinator as members of the QIN Steering Committee (other NCI
staff members may be
invited to participate in the Steering Committee teleconferences and semi-annual
meetings as non-voting members);

Making recommendations on overall project directions within
the network and recommend allocation of funds;

Coordination and facilitation of the interactions and
information sharing among the individual investigators and participating
institutions, and serving as liaison between the Steering Committee and
individual research teams as needed;

Assisting the Steering Committee in developing operating
policies and procedures, and assuring that those policies are acceptable to the
NCI and consistent with NIH policies and federal regulations;

Reviewing the progress of individual research teams;

Participation of the NCI staff members as collaborators in
some shared activities, as appropriate; and

Assisting the network teams as a resource for stimulating
their broader interaction with other NCI and NIH programs to accelerate the use
of quantitative imaging as a measure of therapy response.

2.A.3. Collaborative Responsibilities

A Steering Committee (SC) will be the main governing board
for the network. The SC will be jointly established by the lead PD/PIs of the
awarded multi-disciplinary teams and selected NCI staff members.

The SC will consist of the following voting members:

Two
representatives from each awarded team (one from the clinical center and the
other from the basic science group, e.g., respective lead PD/PIs), who will
collectively have a single vote for each team; and

Two designated
NCI Program staff members (Project Scientist and Coordinator), who will
collectively have one vote for the NIH.

Additional NCI and/or NIH program staff members
and/or program staff members from other federal agencies (e.g., FDA, National
Institute of Standards and Technology [NIST], Department of Defense [DoD]) may be added to the SC by majority vote
of the existing voting committee members to serve in advisory capacity (without voting rights).

The SC may, by majority vote, add representatives from the
imaging and pharmaceutical industries and scientific societies to act in an
advisory capacity to the SC to encourage the development of consensus methods
for imaging protocols and analysis methods and related standards -- This
advisory group may be invited to SC meetings when appropriate.

The SC will elect one of the team investigators as its chair
for a 1-year term annually during the period of the program.

The SC will
have primary responsibility for the overall organizational oversight of the QIN
and for reviewing the research goals among the teams. These responsibilities
will include the following:

Review progress
of each team to make recommendations that encourage intra-team collaborations
to enhance progress and consensus on validation methods;

Review and
facilitate the efforts aimed at sharing of validation methods and related databases
across the Network;

Ensure that team
members take advantage of resources provided by caBIG, NCIA, and the XIP
imaging workstation or alternative commercial informatics solutions for
interoperability of image and meta-data, and related open source tools;

Schedule and
organize semi-annually meetings at which network members will present their
scientific progress and future plans;

Schedule monthly
telephone conference calls to coordinate the activities of the network; and

All SC decisions
and recommendations that require voting will be based on a majority vote.

2.A.4.
Arbitration Process

Any
disagreements that may arise in scientific or programmatic matters (within the
scope of the award) between award recipients and the NIH may be brought to
arbitration. An Arbitration Panel composed of three members will be convened.
It will have three members: a designee of the Steering Committee chosen without
NIH staff voting, one NIH designee, and a third designee with expertise in the
relevant area who is chosen by the other two; in the case of individual
disagreement, the first member may be chosen by the individual awardee. This
special arbitration procedure in no way affects the awardee's right to appeal
an adverse action that is otherwise appealable in accordance with PHS
regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be
required to submit the PHS Non-Competing Grant Progress Report, Form 2590,
annually (https://grants.nih.gov/grants/funding/2590/2590.htm)
and financial statements as required in the NIH Grants Policy Statement. This
report should include a comprehensive technical discussion of progress. In
addition to this annual report, all awardees will submit the following items.

Mid-year
progress report: This report does not have to be submitted on form 2590. It
can be submitted directly to the designated Program Director. The technical
section of this report should not exceed 5 pages, and is intended to highlight
interim progress briefly.

List
of publications and presentations: A list of publications, presented papers,
and poster sessions supported by this cooperative agreement will be submitted
to the SC on a quarterly basis.

Publications:
Copies of each Center publication supported by this grant will be sent to the
SC upon acceptance by a journal.

A final
progress report, invention statement, and Financial Status Report (FSR) are
required when an award is relinquished when a recipient changes institutions or
when an award is terminated.

Section
VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall into
three areas: scientific/research; peer review; and financial or grants
management issues.

Human Subjects Protection:Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (https://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their
institutions, on issues related to institutional policies and
local IRB rules, as well as local, State and Federal laws and regulations,
including the Privacy Rule. Reviewers will consider the data sharing plan
but will not factor the plan into the determination of the scientific merit or
the impact/priority score.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH
Guide NOT-OD-07-088. For additional information,
see https://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model organisms
for biomedical research (see https://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH
recognizes the rights of grantees and contractors to elect and retain title to
subject inventions developed with Federal funding pursuant to the Bayh Dole Act
(see the NIH Grants Policy Statement https://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators
submitting an NIH application or contract proposal, beginning with the October
1, 2004 receipt date, are expected to include in the application/proposal a
description of a specific plan for sharing and distributing unique model
organism research resources generated using NIH funding or state why such
sharing is restricted or not possible. This will permit other researchers to
benefit from the resources developed with public funding. The inclusion of a
model organism sharing plan is not subject to a cost threshold in any year and
is expected to be included in all applications where the development of model
organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are (1) first
produced in a project that is supported in whole or in part with Federal funds
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to
place data collected under this funding opportunity in a public archive, which
can provide protections for the data and manage the distribution for an
indefinite period of time. If so, the application should include a description
of the archiving plan in the study design and include information about this in
the budget justification section of the application. In addition, applicants
should think about how to structure informed consent statements and other human
subjects procedures given the potential for wider use of data collected under
this award.

Inclusion of Women, Minorities, and Children:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the
updated Guidelines is available at https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates:
the use of an NIH definition of clinical research; updated racial and ethnic
categories in compliance with the new OMB standards; clarification of language
governing NIH-defined Phase III clinical trials consistent with the new PHS
Form 398; and updated roles and responsibilities of NIH staff and the
extramural community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or protocols
must provide a description of plans to conduct analyses, as appropriate, to
address differences by sex/gender and/or racial/ethnic groups, including
subgroups if applicable; and b) investigators must report annual accrual and
progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic
group differences.

Inclusion of Children as Participants in Clinical
Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them. All investigators proposing research involving
human subjects should read the "NIH Policy and Guidelines" on the
inclusion of children as participants in research involving human subjects (https://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject
Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH
Public Access Policy Requirement:In accordance with the NIH Public Access Policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html),
investigators must submit or have submitted for them their final, peer-reviewed
manuscripts that arise from NIH funds and are accepted for publication as of
April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be
made publicly available no later than 12 months after publication. As of May
27, 2008, investigators must include the PubMed Central reference number when
citing an article in NIH applications, proposals, and progress reports that
fall under the policy, and was authored or co-authored by the investigator or
arose from the investigators NIH award. For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable
Health Information:The Department of Health
and Human Services (DHHS) issued final modification to the "Standards for
Privacy of Individually Identifiable Health Information", the
"Privacy Rule", on August 14, 2002. The Privacy Rule is a federal
regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable health
information, and is administered and enforced by the DHHS Office for Civil
Rights (OCR).

Decisions about
applicability and implementation of the Privacy Rule reside with the researcher
and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the
Privacy Rule, including a complete Regulation Text and a set of decision tools
on "Am I a covered entity?" Information on the impact of the HIPAA
Privacy Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts can be
found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant
Applications or Appendices:
All applications and proposals for NIH funding
must be self-contained within specified page limitations. For publications
listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless
otherwise specified in this solicitation, Internet addresses (URLs)
should not be used to provide any other information necessary for
the review because reviewers are under no obligation to view the Internet
sites. Furthermore, we caution reviewers that their anonymity may be
compromised when they directly access an Internet site.

Healthy People 2010:The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.

Authority
and Regulations:This program is described in the Catalog of Federal Domestic
Assistance at http://www.cfda.gov/ and is not
subject to the intergovernmental review requirements of Executive Order 12372.
Awards are made under the authorization of Sections 301 and 405 of the Public
Health Service Act as amended (42 USC 241 and 284) and under Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the
terms and conditions, cost principles, and other considerations described in
the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at https://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

Loan Repayment Programs:NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical,
pediatric, contraception, infertility, and health disparities related areas.
The LRP is an important component of NIH's efforts to recruit and retain the
next generation of researchers by providing the means for developing a research
career unfettered by the burden of student loan debt. Note that an NIH grant is
not required for eligibility and concurrent career award and LRP applications
are encouraged. The periods of career award and LRP award may overlap providing
the LRP recipient with the required commitment of time and effort, as LRP
awardees must commit at least 50% of their time (at least 20 hours per week
based on a 40 hour week) for two years to the research. For further
information, please see: http://www.lrp.nih.gov/.